There are controversial results concerning the prognostic implication of TERT promoter mutation in glioma patients concerning MGMT status. In this meta-analysis, we investigated whether there are any interactions of these two genetic markers on the overall survival (OS) of glioma patients. Electronic databases including PubMed and Web of Science were searched for relevant studies. Hazard ratio (HR) and its 95% confidence interval (CI) for OS adjusted for selected covariates were calculated from the individual patient data (IPD), Kaplan-Meier curve (KMC), or directly obtained from the included studies. A total of nine studies comprising 2819 glioma patients were included for meta-analysis. Our results showed that TERT promoter mutation was associated with a superior outcome in MGMT-methylated gliomas (HR = 0.73; 95% CI = 0.55–0.98; p-value = 0.04), whereas this mutation was associated with poorer survival in gliomas without MGMT methylation (HR = 1.86; 95% CI = 1.54–2.26; p-value < 0.001). TERT-mutated glioblastoma (GBM) patients with MGMT methylation benefited from temozolomide (TMZ) treatment (HR = 0.33; 95% CI = 0.23–0.47; p-value < 0.001). MGMT methylation was not related with any improvement in OS in TERT-wild type GBMs (HR = 0.80; 95% CI = 0.56–1.15; p-value = 0.23). The prognostic value of TERT promoter mutation may be modulated by MGMT methylation status. Not all MGMT-methylated GBM patients may benefit from TMZ; it is possible that only TERT-mutated GBM with MGMT methylation, in particular, may respond.

中文翻译：

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TERT启动子突变与MGMT启动子甲基化对神经胶质瘤患者总体生存的相互作用：荟萃分析。

关于胶质瘤患者中MGMT状态的TERT启动子突变的预后意义，存在有争议的结果。在这项荟萃分析中，我们调查了这两种遗传标记物对神经胶质瘤患者的总生存期（OS）是否存在任何相互作用。搜索包括PubMed和Web of Science在内的电子数据库以进行相关研究。根据个别患者数据（IPD），Kaplan-Meier曲线（KMC）或直接从纳入的研究中计算出针对特定协变量调整的OS的危险比（HR）及其95％置信区间（CI）。包括2819例神经胶质瘤患者在内的总共9项研究被纳入荟萃分析。我们的结果表明，TERT启动子突变与MGMT甲基化神经胶质瘤的优异结局相关（HR = 0.73； 95％CI = 0.55-0.98； p值= 0.04），而这种突变与没有MGMT甲基化的神经胶质瘤生存较差有关（HR = 1.86； 95％CI = 1.54–2.26； p值<0.001）。TERT突变的胶质母细胞瘤（GBM）伴有MGMT甲基化的患者受益于替莫唑胺（TMZ）治疗（HR = 0.33； 95％CI = 0.23-0.47； p值<0.001）。在TERT野生型GBM中，MGMT甲基化与OS的任何改善无关（HR = 0.80； 95％CI = 0.56-1.15； p值= 0.23）。TERT启动子突变的预后价值可以通过MGMT甲基化状态来调节。并非所有MGMT甲基化的GBM患者均可从TMZ中受益；特别是只有带有MGMT甲基化的TERT突变的GBM才可能响应。TERT突变的胶质母细胞瘤（GBM）伴有MGMT甲基化的患者受益于替莫唑胺（TMZ）治疗（HR = 0.33； 95％CI = 0.23-0.47； p值<0.001）。在TERT野生型GBM中，MGMT甲基化与OS的任何改善无关（HR = 0.80； 95％CI = 0.56-1.15； p值= 0.23）。TERT启动子突变的预后价值可以通过MGMT甲基化状态来调节。并非所有MGMT甲基化的GBM患者均可从TMZ中受益；特别是只有带有MGMT甲基化的TERT突变的GBM才可能响应。TERT突变的胶质母细胞瘤（GBM）伴有MGMT甲基化的患者受益于替莫唑胺（TMZ）治疗（HR = 0.33； 95％CI = 0.23-0.47； p值<0.001）。在TERT野生型GBM中，MGMT甲基化与OS的任何改善无关（HR = 0.80； 95％CI = 0.56-1.15； p值= 0.23）。TERT启动子突变的预后价值可以通过MGMT甲基化状态来调节。并非所有MGMT甲基化的GBM患者均可从TMZ中受益；特别是只有带有MGMT甲基化的TERT突变的GBM才可能响应。TERT启动子突变的预后价值可以通过MGMT甲基化状态来调节。并非所有MGMT甲基化的GBM患者均可从TMZ中受益；特别是只有带有MGMT甲基化的TERT突变的GBM才可能响应。TERT启动子突变的预后价值可以通过MGMT甲基化状态来调节。并非所有MGMT甲基化的GBM患者均可从TMZ中受益；特别是只有带有MGMT甲基化的TERT突变的GBM才可能响应。